Our work continues to focus on two approaches to hematopoietic differentiation. First, we demonstrated previously that expression of a c-myc or c-myb transgene reversibly blocks terminal differentiation of a mouse erythroleukemia cell line. We are now using this system to test mutant c-myb transgenes so that we can begin to understand how c-myb affects proliferation and differentiation. Our long term goal remains the same, i.e. to understand the mechanisms which are responsible for the apparent inability of most malignant tumors to differentiate. Second, we have developed a general method for subtractive cloning by incorporating polymerase chain reaction (PCR) technology into the preparation and analysis of subtractive CDNA libraries. We have used this novel methodology to identify genes which are expressed in most murine plasmacytomas but rarely in B lymphomas. Thus far, we have identified two classes of genes having this property: 1) two genes are expressed in most plasmacytoma and pre-B lymphoma cell lines; and 2) five genes are expressed in most plasmacytoma cell lines but not in any of the 10 pre-B lymphoma lines examined. Our long term goal for this project is to identify the genes which determine the phenotypes of plasmacytomas and terminally differentiated plasma cells.